tbuckley/cabot-search huggingface dataset:
The BC Generations Project as a tumor tissue resource for cancer research.
Authors: Umaimah Zanif, Parveen Bhatti, Jessica Chu, Jonathan Simkin, Trevor Dummer, Eric Belanger
Journal: Journal of Clinical Oncology (2022)

e22512 Background: Population-based cohort studies can be a resource for tumor specimens, annotated with demographic, lifestyle, and health history data, that support innovative studies of cancer. These data are increasingly important for clinical studies as they can be useful predictors of prognosis and treatment response (1,2) Our aim was to establish and test a process for accessing tumor samples, held at pathology laboratories around British Columbia (BC), for participants of the BC Generations Project (BCGP). Methods: Through the BC Cancer Registry, pathology reports linked with each BCGP solid cancer case were manually reviewed to extract information (e.g., location of pathology laboratory, sample type (i.e., biopsy or excision), and accession number) needed to request tumor samples. From among the successfully abstracted pathology reports, we randomly selected a total of 200 breast, lung, bladder, and pancreatic cancer cases for which to attempt retrieval of formalin-fixed, paraffin-embedded (FFPE) blocks from pathology laboratories across BC. We selected these cancer sites as they capture a representative range of cancer characteristics (e.g., tumor sizes) with which to evaluate the effectiveness of our access process. Results: We successfully identified pathology reports for 1,100 (93%) of the 1,180 incident solid cancer cases diagnosed in BCGP as of 2019 and we successfully retrieved 183 (92%) of the 200 FFPE that we requested from pathology laboratories. No important differences in retrieval rates by cancer site, sample location (Greater Vancouver vs. Outside Greater Vancouver), sample type (biopsy vs. excision) or year of diagnosis were identified. Conclusions: This linkage exercise demonstrates the tremendous potential for BCGP to serve as a population-based resource for highly annotated tumor tissue samples. A text mining solution recently implemented by the Registry will allow us to automate the process for data abstraction and should capture pathology reports for 100% of all newly diagnosed BCGP cancer cases moving forward. This will further enhance the utility of BCGP as a high-quality tumor tissue research resource. References: Lugo D, Pulido AL, Mihos CG, Issa O, Cusnir M, Horvath SA, Lin J, Santana O. The effects of physical activity on cancer prevention, treatment and prognosis: A review of the literature. Complement Ther Med 2019; 44:9–13. Peppone LJ, Mustian KM, Morrow GR, Dozier AM, Ossip DJ, Janelsins MC, Sprod LK, McIntosh S. The Effect of Cigarette Smoking on Cancer Treatment–Related Side Effects. The Oncologist 2011; 16:1784–92.
Venous segmental resection in locally advanced pancreatic tumors.
Authors: Yuriy A. Gevorkyan, Oksana V. Katelnitskaya, Oleg I. Kit, Andrey A. Maslov, Natalya V. Soldatkina, Dmitriy S. Petrov, Vladimir E. Kolesnikov, Dmitriy A. Savchenko, Roman E. Tolmakh, Andrey V. Dashkov, Sergei A. Ilchenko, Vladimir S. Trifanov, Evgeniy N. Kolesnikov
Journal: Journal of Clinical Oncology (2022)

e16243 Background: Surgical treatment is considered the main treatment for pancreatic cancer improving the patient survival. The most common obstacle to surgery with R0 resection is the involvement of the great vessels. Recently, venous resections have been increasingly performed for this type of tumors. Our purpose was to evaluate radicality of surgical treatment and postoperative morbidity in patients with locally advanced pancreatic cancer. Methods: The study included patients with locally advanced pancreatic cancer (T3 N0-1 M0) with damage to the venous segment (portal vein system) confirmed by CT angiography. Results: Over a 5-year period, 73 (18.9%) of 386 operated-on patients with pancreatic cancer underwent surgeries for pancreatic ductal adenocarcinoma with venous resection. The frequency of wedge venous resection was 24.7% (18), segmental resection with end-to-end anastomosis - 46.6% (34), prosthetics - 26% (19), prosthetics with replantation of the splenic vein - 2.7% (2). The postoperative morbidity rate was 30.1%. Within 30 days after surgery, the mortality rate reached 5.5% (4 patients). The main causes were bleeding and thrombosis of the reconstruction area. Only patients with venous segment replacement developed thrombotic complications. Microscopically complete resection was performed in 87.7% of cases (64 patients). During the follow-up period, the 1-year survival rate reached 90%, and the recurrence-free rate was 93%. Conclusions: Surgical treatment for locally advanced pancreatic tumors with damage to the portal vein system shows an acceptable rate of postoperative complications due to the vascular stage, and a high rate of reaching a negative resection margin. Initial assessment of the need for venous resection is required in patients with pancreatic tumors, as well as expanding the extent of surgical intervention due to venous resection to achieve R0 resections.
Factors associated with death from lymphoma in a single center study.
Authors: Helen Ma, Joni Ricks-Oddie, Elani Streja, Ann Eapen, Pankaj Gupta
Journal: Journal of Clinical Oncology (2022)

e19566 Background: It is well known that age, stage, and performance status are important prognostic factors in predicting survival of patients diagnosed with lymphoid malignancies. At the VA Healthcare System, many patients have comorbidities and poor performance status. We evaluated the association of clinical outcomes with lymphoma stage, subtype and performance status in US Veterans. Methods: This retrospective study included patients diagnosed with a lymphoid malignancy including diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and peripheral T-cell lymphoma (PTCL) from January 2008 - December 2021 at the VA Long Beach Healthcare System (n = 221). Endpoints included clinically relevant hematological and non-hematological adverse events (AE), and death from lymphoma (with death from other causes as competing events). Variables of interest included aggressive lymphomas (DLBCL and PTCL, n = 85) vs indolent lymphomas (CLL, FL, MZL and MCL, n = 149), stage (early [0-2] vs advanced [3-4]), age at diagnosis (continuous variable), and performance status (Eastern Cooperative Oncology Group [ECOG] scale: good [0-2] vs poor [3-4]). Logistic regression and Cox models with Fine and Gray competing risk were performed. Results: In patients receiving first line therapy, performance status, disease type, stage, and age at diagnosis did not predict development of clinically relevant AEs with an odds ratio [OR] of 4.1 (p = 0.12, 95% CI 0.70-24), 0.36 (p = 0.06, 95% CI 0.12-1.0), 1.5 (p = 0.39, 95% CI 0.58-4.0), and 1.0 (p = 0.12, 95% 0.99-1.1), respectively. Patients with worse performance status (ECOG 3-4) and advancing age did not have a statistically higher risk of dying from lymphoma vs other causes: performance status: HR 1.7, p = 0.26, 95% CI 0.67-4.3 and age: HR 1.02, p = 0.11, 95% CI 1.0-1.1. In a multivariate analysis, patients with more advanced stage and aggressive subtype were more likely to die from lymphoma vs other causes (hazard ratio [HR] 4.1; p &lt; 0.001, 95% CI 2.2-7.8 and 3.1; p = &lt; 0.0001, 95% CI 1.7-5.5), respectively. Conclusions: The fact that performance status may not predict the development of AEs with first line therapy for lymphoid malignancies is relevant to clinical decision making. However, our findings need confirmation in larger prospective studies.
Polymorphism rs4673 and plasma paraoxonase 1 level for prediction and early diagnosis of anthracycline-mediated cardiotoxicity in patients with breast cancer.
Authors: Dmitry Yu. Gvaldin, Natalya N. Timoshkina, Larisa N. Vashchenko, Tatiana V. Ausheva, Aleksandr B. Sagakyants, Oksana G. Shulgina, Irina R. Dashkova, Emma E. Kechedzhieva, Liubov Yu Vladimirova
Journal: Journal of Clinical Oncology (2022)

12077 Background: Anthracyclines are highly effective chemotherapeutic agents, used for a wide variety of malignancies. Despite their antitumor efficacy there is a risk of cardiotoxic manifestations that reduce the time and quality of life of patients. The purpose was to study the effectiveness of molecular genetic tests based on rs4673 CYBA genotyping (c.242C &gt; T) and measurement of plasma paraoxonase 1 (PON1) level in patients with breast cancer (BC) for predicting and diagnosing anthracycline-mediated cardiotoxicity (AMC). Methods: The study included 256 Caucasian patients (median age - 55 years) with a diagnosis of breast cancer normal cardiovascular system parameters at baseline, who were treated with anthracyclines in 2019-2020. For rs4673 genotyping, DNA was extracted from the blood by using DNA-sorb-B (AmpliSens, Russia). HRM-PCR was performed on a CFX96 amplifier (Bio-Rad, USA). The presence of polymorphism was confirmed by the Sanger method on a Genetic Analyzer 3500 (ABI, USA). The concentration of PON1 in blood plasma was measured at baseline and after 4 course of chemotherapy with anthracyclines using ELISA kits (Cloud-Clone Corp., China/USA). Results: During the follow-up period 21 (8.2%) patients developed signs of subacute (changes developed within several weeks after the last course of therapy) or early chronic AMC (changes developed within a year after completion of anthracycline therapy). In the group of patients without AMC the frequency of the minor allele rs4673 (c.214C &gt; T CYBA) was 0.38, the frequency of genotypes C/C was 0.4, C/T - 0.43, and T/T - 0.17. The risk of AMC increased by 6.49 times in the presence of the rs4673 polymorphic allele (p = 0.002). The area under the ROC curve of the test based on rs4673 genotyping was 71.9%. The concentration of PON1 after the 4 courses of chemotherapy increased by 19.57% in the group of patients without cardiotoxic manifestations (p = 0.018) and in the group of patients with AMC by 20.23% (p = 0.007) as compared to the initial level. Besides, after 4 courses of chemotherapy the PON1 level was higher in patients with AMC by 25.08% (p = 0.026) than in patients without cardiovascular complications. The sensitivity of the test based on the measurement of the PON1 level in the blood plasma after 4 courses of chemotherapy was 100%, the specificity was 70.8% with a cut-off value of 2.9 ng/ml. Conclusions: This study has showed that genotyping of patients for the rs4673 polymorphism allows pre-stratification of the risk group white determination of the PON1 level in blood plasma after 4 courses of chemotherapy gives the opportunity to identify patients with AMC and promptly correct the chosen treatment.
Robot-assisted PSMA-radioguided salvage surgery in recurrent prostate cancer using a DROP-IN gamma probe - a prospective feasibility study
Authors: H.A. De Barros, M.N. Van Oosterom, M.L. Donswijk, J.J.M.A. Hendrikx, A.N. Vis, T. Maurer, F.W.B. Van Leeuwen, H.G. Van Der Poel, P.J. Van Leeuwen
Journal: European Urology (2022)
The prognostic value of peripheral blood inflammatory indices early variation in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with nivolumab (Δ-Meet-URO analysis).
Authors: Sara Elena Rebuzzi, Alessio Signori, Sebastiano Buti, Giuseppe Luigi L. Banna, Marco Stellato, Daniele Santini, Umberto Basso, Ugo De Giorgi, Silvia Chiellino, Alessia Salfi, Paolo Andrea Zucali, Cristina Masini, Emanuele Naglieri, Giuseppe Procopio, Michele Milella, Francesco Boccardo, Lucia Fratino, Stefania Pipitone, Camillo Porta, Giuseppe Fornarini
Journal: Journal of Clinical Oncology (2022)

4534 Background: Immunotherapy has improved the treatment landscape of mRCC pts and identifying biomarkers for patients’ selection is clinically needed. Inflammatory indices from peripheral blood showed a prognostic value in different tumors and therapies, including immunotherapy. These biomarkers are inexpensive and readily available in clinical practice. We aimed to assess the prognostic role of the dynamic evaluation of these indices in immunotherapy-naïve pretreated mRCC pts. Methods: The Meet-URO 15 multicentric retrospective study enrolled 571 pretreated mRCC pts receiving nivolumab. The Δ-Meet-URO was a secondary analysis on the early variation through the first four cycles of therapy compared with baseline (difference, delta - Δ) of white blood cells, platelets and inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII, platelets x NLR), their comparison with baseline values and correlation with treatment response, overall (OS) and progression-free survival (PFS). The baseline and Δ cut-offs were identified by ROC curves for OS. Results: The analysis was performed on 422 mRCC pts (74% of the entire cohort). Patients with ΔNeutrophils &lt; 730 at 2 nd , 3 rd and 4 th cycles were more responders ( p &lt; 0.001, p = 0.003 and p &lt; 0.001) with longer mPFS (11 vs 6.1 months, p = 0.033) and mOS (46.9 vs 20.8 months, p = 0.046) compared to ΔNeutrophils ≥ 730. There was a significant interaction between baseline and ΔNeutrophils on PFS ( p = 0.047). Pts with baseline neutrophils ≥ 4330/mm 3 had longer mPFS when ΔNeutrophils &lt; 730 ( p = 0.002), whilst no difference was observed in those pts with baseline neutrophils &lt; 4330/mm 3 according to ΔNeutrophils ( p = 0.46). Similar non-significant trends were observed in mOS. Patients with ΔNLR &lt; 0.5 at 3 rd and 4 th cycles were more responders ( p = 0.004 and p = 0.001, respectively) with doubled mPFS (12.1 vs 6.4 months, p = 0.007) and mOS (46.9 vs 21.7 months, p = 0.062) compared to ΔNLR ≥ 0.5. No significant interaction between baseline NLR and ΔNLR was observed in PFS and OS, suggesting a similar association between ΔNLR and PFS or OS, regardless of the baseline NLR cut-off of 3.2. The multivariable analyses confirmed all these results. Conclusions: The early assessment of NLR and neutrophils variations during immunotherapy for mRCC pts is a promising, affordable and non-invasive prognostic tool. Prospective and external validation analyses are warranted.
Relationship between systemic inflammatory response markers and immune treatment related toxicity (IrAEs) in hepatocellular carcinoma (HCC).
Authors: Sirish Dharmapuri, Umut Ozbek, Anwaar Saeed, Mahvish Muzaffar, Suneetha Amara, Nicola Personeni, Tiziana Pressiani, Naoshi Nishida, Sonal Paul, Dominik Bettinger, Uqba Khan, Petros Fessas, Yi-Hsiang Huang, Ahmed Omar Kaseb, Anjana Pillai, Lorenza Rimassa, David J. James Pinato, Celina Ang
Journal: Journal of Clinical Oncology (2022)

e16204 Background: A well-recognized class effect of immune check point inhibitors (ICI) is IrAEs ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI. Treatment related deaths are reported in ̃5% of patients (pts) treated with ICI. There are, however, no reliable markers to predict the onset &amp; severity of IrAEs. We tested the association between neutrophil-lymphocyte ratio (NLR) &amp; platelet-lymphocyte ratio (PLR) at baseline with development of clinically significant IrAE (graded ≥2) in HCC pts treated with ICI. Methods: Data was extracted from a large international database from a consortium of 11 tertiary-care referral centers located in the USA, Europe &amp; Asia. NLR=Absolute neutrophil count/ Absolute lymphocyte count (ALC) &amp; PLR=Platelet count/ALC. A cutoff of 5 for was used NLR &amp; 300 for PLR based on literature. We also tested the association between antibiotic &amp; steroid exposure to IrAEs. Results: Clinical data was collected from 361 pts treated between 2016–2020 across the USA (66%), Asia (12%) &amp; Europe (22%) in this multinational database. Most pts received Nivolumab monotherapy (n=318, 74%). 167 (46%) pts developed at least one IrAE, highest grade 1 in 80 (48%), grade ≥2 in 87(52%) pts. Baseline characteristics did not differ significantly between the groups (Table). In a univariable regression model to predict grade ≥2 IrAEs, a PLR &gt;300 was associated with a lower incidence of clinically significant IrAEs (OR = 0.40; p=0.044). NLR &gt;5 was associated with a trend toward lower incidence of clinically significant IrAEs (OR = 0.58; p=0.097). Multivariate analyses confirmed PLR as independent predictive marker of grade ≥2 IrAEs (OR = 0.24; p=0.007). Antibiotics use was not associated with IrAE incidence (OR = 1.02; p=0.954). Steroid use was associated with a &gt;2-fold higher incidence of grade ≥2 IrAEs (OR = 2.74; p&lt;0.001), though it may be noted that 37% of pts received steroids for treatment of IrAEs. Conclusions: Lower NLR &amp; PLR may predict the appearance of IrAEs in HCC treated with ICI, although this conclusion warrants prospective validation. This finding is in keeping with several studies that showed improved survival in pts who develop of IrAEs &amp; have a lower NLR &amp; PLR.[Table: see text]
Will COVID-19 directives to reduce regularly scheduled physical examinations affect recurrence detection in patients with early breast cancer?
Authors: Ana-Alicia Beltran-Bless, Bader Alshamsan, Mashari J. Alzahrani, John Frederick Hilton, Vicky Samuel, Kelly-Anne Baines, Gregory Russell Pond, Lisa Vandermeer, Mark J. Clemons, Gail Larocque
Journal: Journal of Clinical Oncology (2022)

1532 Background: The COVID-19 pandemic has significantly reduced routinely scheduled in person assessment and examination of early breast cancer patients (EBC). To assess if this is likely to impact the detection of recurrent disease, we reviewed recurrence patterns of EBC patients enrolled in a survivorship program that adheres to ASCO guidelines. Methods: Charts of EBC patients transferred through a single center Wellness Beyond Cancer Program (WBCP) and who subsequently had a breast cancer recurrence between February 1, 2013 and January 1, 2019 were reviewed. Patient, tumor and treatment characteristics were evaluated. Results: Of 206 patients eligible for the current study, 41 patients had ipsilateral breast recurrences (19.9%), 135 had distant recurrences (65.5%) and 30 had contralateral new breast cancers (14.6%). Ipsilateral breast recurrences were detected by the patient in 53.7% (22/41) and by routine imaging in 41.5% (17/21). The majority of distant recurrences (125/135, 92.6%) were detected via patient-reported symptoms. Contralateral breast primaries were detected by patients 16.7% (5/30) or by routine imaging (83.3%, 25/30). Only 2/206 (1.14%) recurrences/new primaries were detected by healthcare providers at routinely scheduled follow-up visits. There was a statistical difference in recurrence detection between image detected vs. self-detected in the following factors: grade 3 (26.5% vs 51%, p &lt; 0.007), triple negative breast cancer (3.9% vs. 15.1%, p = 0.03), HER2 disease (18.4% vs. 9.8%, p = 0.04). Conclusions: Despite following ASCO follow-up guidelines for routinely scheduled follow-up appointments with physical examination, healthcare providers rarely detect recurrence disease. While reduced in person visits may affect other aspects of follow-up (e.g., toxicity management), it appears unlikely, provided patients attend regular screening tests, that reduced in-person follow-up is associated with worse breast cancer-related outcomes during the COVID-19 pandemic. [Table: see text]
Safety, tolerability, pharmacokinetics and preliminary efficacy of MIL93, an anti-Claudin18.2 monoclonal antibody, in patients with advanced solid tumors: A phase 1 clinical study.
Authors: Jing Huang, Bo Zhang, Ying Wang, Feng Wang, Shikai Wu, Yi Zheng, Jianping Xu, Dongmei Lan, Min Wei, Sijun Liu
Journal: Journal of Clinical Oncology (2022)

3086 Background: Claudin18.2 (CLDN18.2) is specifically expressed in the tight junction of gastric epithelial cells, and has been identified as a promising target in gastric and pancreatic cancer as well as several other malignancies. MIL93 is a humanized IgG1 monoclonal antibody targeting CLDN18.2. From January 2021, we started a multicenter, dose escalation and expansion phase 1 study of MIL93, for the treatment of patients with advanced solid tumors (Protocol number MIL93-CT101, Beijing Mabworks Biotech Co. Ltd.) at 6 clinical study sites in China. Currently the study is still ongoing. Methods: We already enrolled 13 pts aged 18 years or older with advanced solid tumors whose disease had progressed after standard systemic treatments. Pts were required to have measurable lesion as per RECIST v1.1; ECOG PS score of 0-1 and adequate organ functions. In the dose escalation phase, 6 dose levels (0.3mg/kg, 1mg/kg, 3mg/kg, 10mg/kg, 20mg/kg and 30mg/kg, Q3W) of MIL93 were planned for assessment. Accelerated titration was adopted for the first 2 dose levels, and the 3+3 design was used afterwards. In the dose expansion phase, pts with CLDN18.2-positive cancers received the selected RP2D. The primary objectives were the safety and tolerability, dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of MIL93. Secondary objectives included pharmacokinetics, immunogenicity and preliminary efficacy. Results: At the data cut-off date (February 14, 2022), 13 pts were enrolled between April 23, 2021 and February 9, 2022. MIL93 was well-tolerated for the dosages tested (0.3mg/kg through 20mg/kg Q3W) as no DLTs were observed, and dose escalation was ongoing at 30mg/kg. In particular, Grade 3 nausea and vomiting occurred in 2 cases in the third dose group, so preventive antiemetic treatment was given from the fourth dose group. 9 pts (69.2%) experienced at least one treatment-emergent adverse event (TEAE) with no Grade 4 or Grade 5 AEs. The most common treatment-related adverse events (TRAEs) occurring in ≥10% of pts were nausea (46.2%), vomiting (46.2%), fatigue (15.4%), anemia (15.4%). Serious adverse events (SAEs) were observed in 3 (23.1%) pts, and MIL93-related SAEs occurred in 1 pt (7.7%, Grade 3 nausea). Among the 10 pts who had at least one post-treatment radiological evaluation, 1 pt with CLDN18.2-positive gastric cancer achieved PR and 3 pts had SD, including 1 case of gastric cancer, 1 case of gastroesophageal junction cancer and 1 case of gallbladder cancer. Conclusions: MIL93 had a favorable safety profile with no DLTs observed through 20mg/kg Q3W. Pts with CLDN18.2-positive gastric cancer responded to the treatment. Dose escalation and expansion in selected tumor types is currently underway. Clinical trial information: NCT04671875.